Periodontics
Rui Vicente Oppermann(a) Patricia Weidlich(a) Marta Liliana Musskopf(b)
(a)Department of Periodontology, School of
Dentistry, Univ Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
(b)Graduate Program in Dentistry, School of
Dentistry, Univ Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Corresponding Author:
Rui Vicente Oppermann
E-mail: ruioppermann@gmail.com
Periodontal disease and systemic
complications
*Abstract: Periodontal diseases comprise a number of infectious and in-lammatory conditions brought about by the interaction between supra-gingival and subsupra-gingival bioilms and the host inlammatory response. Periodontal diseases should be considered systemic conditions. This means that they are both modulated by the body’s systems and play a role as a risk factor for systemic derangements. The current evidence sup-ports some of these interactions, such as smoking as a risk factor for peri-odontal disease and diabetes mellitus, as both inluenced by and inlu-encing inlammatory changes in the periodontal tissue. Other potential associations are still being researched, such as obesity, hormonal chang-es, cardiovascular disease, and adverse outcomes in pregnancy. These, and others, still require further investigation before the repercussions of periodontal disease can be fully elucidated. Nevertheless, at the pres-ent time, the treatmpres-ent of periodontal diseases—and, most importantly, their prevention—enables adequate intervention as a means of ensuring periodontal health.
Descriptors: Periodontal Diseases; Risk Factors; Smoking; Diabetes Mellitus; Cardiovascular Diseases.
Introduction
Periodontal diseases comprise a number of infectious and inlamma-tory conditions brought about by the interaction between supragingival and subgingival bioilms and the host inlammatory response. The very presence of bioilms, of the microorganisms that compose them, and of bacterial metabolites produced following colonization of the subgingi-val area elicits an inlammatory response. Activation of the host immune system, primarily for protective purposes, ultimately results in tissue de-struction by triggering the synthesis and release of cytokines, proinlam-matory mediators, and matrix metalloproteinases. The progression and severity of the periodontal destruction caused by periodontitis depends on the balance between the virulence of the local bioilm and the host immune response.1
Historically recognized interactions
A variety of systemic factors and conditions may interfere with and modulate the relationship between the microbial challenge and the host response. Smoking and diabetes have classically been recognized as risk factors for periodontitis; smokers and diabetics are at higher odds of
de-Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.
Submitted: Nov 30, 2011
Accepted for publication: Jan 24, 2012 Last revision: Aug 20, 2012
veloping periodontitis as compared with individu-als unaffected by either condition.2-6 Furthermore,
longitudinal studies have shown that smokers are at a signiicantly higher risk of periodontal attach-ment loss than are never-smokers.7-9 In a
longitudi-nal study of 101 patients with a 10-year follow-up, Bergström et al.7 found that the progression of
at-tachment loss was signiicantly higher by increased exposure to smoking, after adjusting for age. In a cross-sectional study conducted on a representative sample from the Brazilian city of Porto Alegre and its metro area, moderate and heavy smokers were found to have a higher prevalence and extent of at-tachment loss than mild smokers and non-smokers alike.10 An association was found between
smok-ing and attachment loss, with subjects classiied as “heavy smokers” exhibiting an eightfold risk of at-tachment loss as compared with never-smokers (RR 8.2; 95% CI 5.5–12.2). Calculation of the risk of at-tachment loss attributable to smoking revealed that subjects with a loss of ≥ 5 mm in at least 30% of teeth had a 71% risk of periodontitis attributable to smoking.11 These data suggest that a smoking
ces-sation program would lead to an approximate 12% decrease in periodontitis, which would correspond to 90,000 potential cases in the study population.
The presence of diabetes has also been consis-tently reported as a risk factor for periodontitis in the literature.12,13 In the absence of adequate
glyce-mic control, diabetes changes the host response to the microbial challenge, leading to a greater preva-lence and extent of periodontal disease. U.S. stud-ies carried out in a population of Native Ameri-cans with a high prevalence of type 2 diabetes have shown that diabetics are at a threefold risk of bone loss as compared with healthy subjects (OR 3.43; 95% CI 2.28–5.16).14,15 In the National Health and
Nutrition Examination Survey conducted from 1988 to 1994 (NHANES III), diabetics over the age of 30 exhibited greater attachment loss, prob-ing depth, and gprob-ingival recession and bleedprob-ing than non-diabetics, even after adjusting for age, gender, and ethnicity.16 Likewise, the percentage of
affect-ed teeth (as measuraffect-ed by assessment of four peri-odontal parameters) was approximately twice as high in diabetics as in non-diabetics. In Brazil, the
Porto Alegre study found signiicant differences in the prevalence of attachment loss between diabet-ics (self-reported) and non-diabetdiabet-ics, with a higher prevalence of ≥ 3 mm and ≥ 5 mm loss in the former group.10
In addition to diabetes and smoking, psycho-social factors and socioeconomic status have also been associated with periodontitis. The presence of factors such as stress, depression and anxiety often leads to poorer periodontal health. Stressed, anx-ious, or depressed persons tend to neglect their oral hygiene and often smoke more than usual and eat inadequately. These factors have a negative impact on the immune system.17 A case-control study was
carried out to compare the prevalence of stress, anx-iety, and depression in healthy controls and patients with periodontitis, using questionnaires validated for the Brazilian population. Associations were found between periodontitis and gender, smok-ing status, and educational attainment, whereas no signiicant association was found with any of the psychosocial factors assessed.18 Living in lower
so-cioeconomic strata is also associated with increased rates of periodontal inlammation and attachment loss.19 In the Porto Alegre study, adults of lower
so-cioeconomic status had a greater prevalence and ex-tent of attachment loss, as compared with subjects of higher socioeconomic class.10 The same study
also found that young adults living in underprivi-leged conditions had four times the odds of acquir-ing aggressive periodontitis than did those of higher socioeconomic status.20
New associations worthy of
consideration
modi-ied response to the microbial challenge of periodon-tal disease. A case-control study comparing the clinical periodontal status of patients with Sjögren’s syndrome to that of controls revealed a generally poorer periodontal condition in the former.21
Pa-tients with secondary Sjögren’s syndrome, who have other immune alterations in addition to glan-dular dysfunction, had particularly greater probing depths, attachment loss, and bleeding on probing, as compared with controls. The authors conclude that Sjögren’s syndrome has an adverse effect on periodontal health, insofar as gingival inlammation was more evident in patients with the syndrome, particularly those with secondary Sjögren’s.
Another systemic condition that alters host im-mune response is obesity, which has become a worldwide epidemic. Obesity is known to induce a hyperinlammatory state, with T-lymphocyte and monocyte/macrophage changes that could affect re-sponse to the microbial challenge. A study of over 700 subjects in Southern Brazil found an associa-tion between body mass index and periodontitis in women.22 Obese women had a relative risk of 2.1 for
periodontitis as compared with non-obese women, and, upon multivariate analysis, non-smokers had a 3.4-fold risk of periodontitis as compared to women with a normal body mass index.
The ability of hormones to inluence periodon-tal health is well established. The hormonal changes of puberty, as well as the increased hormone levels of pregnancy, can alter the periodontal inlamma-tory response to a similar bioilm load. The poten-tial effect of menopause, which is characterized by an estrogen deiciency that inluences bone metabo-lism, is a more recent concern. The association be-tween menopause, hormonal replacement therapy, and periodontal attachment loss was investigated by Haas et al. The authors assessed 328 women and found a signiicantly greater rate of periodon-titis in women who were not receiving hormonal replacement therapy as compared with premeno-pausal women (64.4% versus 46.3% respectively, p = 0.005). There was no signiicant difference in periodontitis rate between women receiving hor-mone replacement therapy and premenopausal women (48.8% and 46.3% respectively).23
The effect of periodontal diseases
on other systemic conditions
In 1900, Hunter formally introduced the con-cept of focal disease.24 Ever since then, the interest
in the role of oral infection in diseases and disorders of remote tissues and structures has varied widely. Modern research on oral infection—and, by exten-sion, on intraoral inlammation—as a risk factor for systemic disease began with a 1989 Finnish study that reported an association between oral diseases, tooth loss, and heart disease.25 This observation was
followed by studies on a variety of other potential associations, as well as research into the biological plausibility of these associations, and investigation of mechanisms that might explain potential causal relationships.
Periodontal diseases are of a joint infectious and inlammatory nature. They are characterized by the presence of supra- and subgingival bioilms, which elicit an inlammatory host response. This inlam-mation of periodontal tissue, diagnosed clinically by the presence of marginal bleeding and, particu-larly, by periodontal bleeding and increased probing depth, determines periodontal injury. Periodontal bleeding reveals the ulcerated area of subgingival tissue, whereas probing depth reveals the extent of the area of tissue covered by subgingival bioilm. Al-though different estimates for quantiication of the area of periodontal injury have been reported in the literature, the inlammatory challenge of periodon-tal disease usually consists of an affected area of 15 cm2 to 72 cm2.26 In this setting, the
inlamma-tory burden of untreated periodontal disease is not only present at the local level, but is also associated with the presence of biomarkers of systemic inlam-mation, such as C-reactive protein.27
It bears stressing that any study of the associa-tion between chronic inlammatory condiassocia-tions (such as periodontal disease), cardiovascular disease, and diabetes should necessarily follow the “common risk factor approach”.28 The key concept underlying this
approaches for the control of each condition.
Many studies have investigated the biological plausibility of the association between periodontal disease and systemic disorders. Basically, there are three possible mechanisms whereby periodontal dis-eases may induce a remote inlammatory response:
• bacteremia;
• immune response to the presence of oral patho-gens; and
• hematogenous spread of components of the in-fection/immune response cascade.19
The hypothesis that uses bacteremia to explain the association between periodontal disease and sys-temic conditions is based on the spread of bacteria from the supragingival and subgingival bioilm into the bloodstream through the ulcerated junctional epithelium of the periodontal lesion. Aside from in-vasive procedures such as subgingival scaling and dental extraction, which are known to produce tran-sient bacteremia, daily activities such as brushing and chewing may also lead to dissemination of bac-teria and bacbac-terial products into the bloodstream. A double-blind clinical trial evaluated the presence of bacteremia after brushing and dental extraction and found that both were capable of inducing simi-lar bacteremia.29 Chewing may also lead to release
of endotoxins from subgingival bioilm bacteria into the bloodstream, particularly in patients with ad-vanced periodontitis.30
The host response to oral pathogens may also ex-plain the association between periodontal diseases and other systemic disorders. In one study, systemic levels of interleukin-6, C-reactive protein, and i-brinogen were measured before and 3 months after completion of a course of non-surgical periodontal therapy. The authors found that patients who re-ceived periodontal treatment experienced a signii-cant reduction in levels of all three markers of sys-temic inlammation.31
Hematogenous spread of components of the in-fection/immune cascade constitutes the third po-tential explanation for the relationship between periodontal disease and systemic conditions. In an investigation on the presence of oral bacteria in heart valves and aortic aneurysms, Streptococcus
mutans and Aggregatibacter
actinomycetemcomi-tans were the species of oral bacteria most often
iso-lated from heart specimens.32
Association between periodontal
and cardiovascular disease
Studies on the association between periodon-tal and cardiovascular disease have used biological plausibility to demonstrate how periodontitis could be associated with increased risk of cardiovascu-lar events. One important aspect that should be taken into account is the set of shared risk factors for both.33 Analysis of risk factors such as smoking,
diabetes, obesity, socioeconomic status, gender, sed-entary lifestyle, genetic factors, serological markers, and inlammatory mediators shows that several of these play a role in causation of periodontal and car-diovascular diseases alike.
Five systematic reviews published over the last decade support the presence of an association be-tween periodontal and cardiovascular disease.34-38
The association itself was considered modest, but signiicant. A meta-analysis of cohort, case-control, and cross-sectional studies assessed the prevalence and incidence of coronary heart disease after ad-justment for key factors such as age, gender, smok-ing, and diabetes.38 The pooled results of the cohort
disease are signiicantly higher in persons with poor periodontal health. Periodontal disease could thus be considered a risk factor for coronary heart dis-ease, although prospective studies (assessing the risk reduction of cardiovascular events after treatment of periodontal disease, for instance) are still required for proof of causation.
The association between markers of systemic bacterial exposure secondary to periodontal disease and cardiovascular risk was investigated in a meta-analysis of ive cohort studies and seven cross-sec-tional studies. Assessment of these studies revealed seven investigations on coronary heart disease, four studies on myocardial infarction, and three stud-ies evaluating carotid intima-media thickness as a marker of early-stage atherosclerosis. Bacterial exposure was detected for periodontal pathogens through serology in most studies and through bac-terial load measurement or C-reactive protein levels as a surrogate marker in others. The meta-analysis found that periodontal disease with concomitant el-evation of markers of bacterial exposure was strong-ly associated with coronary heart disease (OR 1.75; 95% CI 1.32–2.34; p < 0.001). Increased intima-me-dia thickness was also found in patients with peri-odontitis (IMT +0.03 mm, 95% CI 0.02–0.04), but no association was found between periodontal dis-ease and myocardial infarction. Beck et al. assessed the relationship between bacterial exposure second-ary to periodontal disease (as measured by levels of IgG antibodies to 17 species of oral bacteria) and cardiovascular disease in 4,846 participants.39 The
authors did indeed ind associations with age, gen-der, smoking status, hypertension, educational at-tainment, and IgG antibodies to oral organisms, but they failed to demonstrate an association between clinical signs of periodontal disease and coronary heart disease. The authors suggest that “the quality and quantity of the host response to oral bacteria may be an exposure more relevant to systemic ath-erothrombotic coronary events than to clinical mea-sures”.39 Another study assessing bacterial load and
its relation to cardiovascular disease made note of one important factor that is consistently associated with both conditions: socioeconomic status.40
So-cioeconomic conditions were associated with a wide
range of variables (higher body mass index, blood pressure, lipid fractions, glycated hemoglobin, lung function, smoking status, and diabetes), but did not correlate with bacterial load. Therefore, bacterial load does not appear to explain the differences in cardiovascular risk proile associated with socioeco-nomic status.
A review of the Brazilian literature highlighted three studies carried out in the country that also re-vealed an association between periodontal and car-diovascular disease.19 A study of 361 patients with
periodontitis and advanced coronary artery block-age found an odds ratio of 2.6 for the association.41
Another cross-sectional study of a sample of 634 patients found poorer periodontal health in subjects with ischemic coronary atherosclerosis.42 The third
study, using a case-control design, found a signii-cant association (OR 5.1) between periodontitis and acute coronary syndrome.43
Attempts have recently been made to elucidate the pathway to increased cardiovascular risk in periodontitis (whether predominantly due to infec-tion or to inlammainfec-tion). A randomized clinical trial compared non-surgical periodontal therapy per-formed with or without adjuvant antibiotics in asso-ciation with clinical variables, gingival luid, blood tests, metalloproteinases, C-reactive protein, and lipid fractions in subjects with both chronic peri-odontitis and coronary artery disease. Both groups experienced reductions in HDL cholesterol and apo-lipoprotein A, but neither group achieved a signii-cant reduction in surrogate markers of myocardial infarction risk.44 Other interventional studies have
been conducted to investigate the association,45,46
using proxy variables (endothelial function, for ex-ample) as cardiovascular outcomes. Periodontal treatment seems to improve some proinlammatory mediators and alters endothelial function, but au-thors suggest that deinitive trials are still needed.
Association between periodontal
disease and adverse outcomes
in pregnancy
development. Preterm birth, deined as delivery before 37 weeks’ gestation, is usually the result of preterm labor, premature rupture of membranes, or maternal or fetal complications.47 Infants are
clas-siied as “low birth weight” (LBW) when weight is lower than 2500 g.
The estimated prevalence of preterm birth rang-es from 6 to 15% across different populations. In the municipality of Porto Alegre, 2007 data from the Liveborn Infant Information System (SINASC) showed prevalence rates of 10.4% for preterm birth and 10.1% for LBW.48
Infant morbidity and mortality decline as gesta-tional age advances. Prematurity accounts for ap-proximately half of all perinatal deaths and half of all congenital neurological deicits. Accordingly, the care of premature infants entails high costs, since they will often require prolonged admission to neo-natal intensive care units and may develop respirato-ry, visual, cardiac, and neurologic sequelae, among other long-term complications, the severity and im-pact of which are directly associated with gestation-al age and birth weight.49,50
The presence of inlammation accounts for a substantial fraction of all preterm births. In most such cases, inlammation is secondary to intrauter-ine infection. However, evidence suggests that re-mote infections, such as appendicitis, pneumonia, and periodontitis, may trigger preterm labor.51-54
The association between periodontal disease and prematurity and/or low birth weight may be ex-plained by three routes, just as the association be-tween periodontal and cardiovascular disease:
• dissemination of the by-products of inlamma-tion through the bloodstream,
• maternal/fetal immune response to the presence of oral pathogens, and
• hematogenous spread of oral bacteria.50,55
Observational studies and clinical trials have assessed the relation between adverse gestational outcomes and periodontal diseases. Indeed, several such studies have been carried out in the Brazilian population.19 Different deinitions of periodontitis,
inadequate adjustment for confounders, and differ-ent methods of measuring outcomes and endpoints
may partially account for the divergence of indings in the literature. Furthermore, distinct populations may not share the same risk factors for these condi-tions; in this context, the speciic biological, socio-economic, and environmental factors of each popu-lation should be taken into account.
Among the various study designs used for this purpose, clinical trials warrant particular atten-tion, insofar as they are able to provide the highest level of scientiic evidence. Lopez et al. (2002) con-ducted a clinical trial of 200 women who received periodontal therapy prior to the 28th gestational
week and 200 women who received periodontal treatment after delivery.56 The primary endpoint
was delivery before 37 weeks’ gestation with a birth weight of < 2500 g. The incidence of prematurity in the experiment group was 1.8%, versus 10.11% in controls. Upon multivariate analysis, the pres-ence of periodontal disease was the main risk fac-tor for prematurity and low birth weight. The same group of investigators carried out another study on 580 pregnant women with gingivitis who received periodontal care before 28 weeks’ gestation (experi-mental group) and 290 pregnant women with gingi-vitis who received treatment after delivery (control group). The primary endpoint was the same as that of the previous study. The incidence of prematurity with low birth weight was 2.4% in the experiment group, versus 6.71% in the control group (OR 3.26; 95% CI 1.56–6.83; p = 0.0009). Logistic regression analysis showed that pregnant women with gingivi-tis are at greater risk of delivering premature, LBW infants (OR 2.76; 95% CI 1.29–5.88; p = 0.008) as compared with women who received gingivitis treat-ment.
These positive results were not conirmed in sub-sequent clinical trials. In 2006, Michalowicz et al.57
published a multi-center clinical trial performed in the United States with 823 pregnant women. Their results demonstrated that periodontal therapy did not alter the occurrence of preterm birth or low birth weight. Recently, two large clinical trials con-ducted in the US58,59 and Australia60 have also failed
planing either in the second trimester of gestation or after delivery. The test group had an incidence of preterm delivery of 13.1% whereas the incidence was 11.5%58 in the control group. Contradictory
results were also observed in recent meta-analyses. Polyzos et al.61 suggested a beneicial effect of
peri-odontal treatment on PTLBW rates, whereas
Fogac-ci et al.62 could not corroborate this inding.
Conclusion
Periodontal diseases should be considered sys-temic conditions. This means that they are both modulated by the body’s systems and play a role as a risk factor for systemic derangements. The current
evidence supports some of these interactions, such as smoking, as a risk factor for periodontal disease, and diabetes mellitus, as both inluenced by and inluencing inlammatory changes in the periodon-tal tissue. Other potential associations are still be-ing researched, such as obesity, hormonal changes, cardiovascular disease, and adverse outcomes in pregnancy. These, and others, still require further investigation before the repercussions of periodontal disease can be fully elucidated. Nevertheless, at the present time, the treatment of periodontal diseas-es—and, most importantly, their prevention—en-ables adequate intervention as a means of ensuring periodontal health.
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